Given the large market potential and high unmet need for new respiratory syncytial virus (RSV) therapies, drug developers have been focused on new vaccine and monoclonal antibody (mAb) development. A vaccine for RSV has yet to be approved anywhere around the globe. However, recent advances in the field have led to the priority review of Pfizer and GSK’s vaccines for older adults, which recently gained positive recommendations from the FDA’s Vaccines and Related Biological Products Advisory Committee. Despite their benefits, new RSV therapies may accelerate the emergence of drug-resistant strains, according to GlobalData.
In November 2022, AstraZeneca/Sanofi’s new mAb, nirsevimab, was also approved for use in infants in the EU and the UK. Prior to the recent developments, AstraZeneca’s Synagis (palivizumab), approved in 1998 to prevent RSV in high-risk infants, was the only approved option and dominated the global RSV market. However, this has caused RSV to mutate, resulting in palivizumab-resistant RSV strains.
Nancy Jaser, Pharma Analyst at GlobalData, comments, “Drug developers and regulators should proceed with extreme caution while bringing new RSV vaccines and mAbs to market, to avoid the potentially serious consequences of inducing novel viral mutations and drug-resistant strains of RSV. As an RNA virus, like SARS-CoV-2, RSV is highly prone to mutations, especially while under pressure from mAbs. Since palivizumab was used widely in infants for over two decades, the emergence of resistant RSV variants is not surprising. However, given the limited therapeutic options, drug-resistant RSV strains may pose a significant threat to public health.”
Antibody-resistant mutations have already been documented in RSV after the administration of AstraZeneca/Sanofi’s new RSV mAb, nirsevimab, despite its very recent approval in only two regions. Increased viral resistance to both palivizumab and nirsevimab leaves high-risk infants in an extremely vulnerable position, without any “guaranteed” protection against RSV.
Nancy continues, “The ongoing COVID-19 pandemic highlighted a major disadvantage regarding the use of mAbs against RNA viruses. mAbs are designed to target a highly specific part of the viral epitope, one capable of changing across variant strains, resulting in a loss of efficacy as the virus evolves. This resulted in numerous authorizations of mAbs being revoked due to lost efficacy against COVID-19 as the virus mutated to evade their attack, foreshadowing the potential of RSV to evolve in a similar manner.”
The possibility of viral escape from nirsevimab is a serious concern, especially as Pfizer and GSK’s RSV vaccines for older adults are expected to gain approval in May 2023. It is unknown if novel vaccines will have any effect regarding resistance to mAbs. Since RSV has not yet circulated through large populations of vaccinated individuals, the widespread viral response of RSV to vaccines remains unpredictable.
Nancy concludes, “Given the lack of vaccines and therapies for high-risk infants, the risks of inducing more drug-resistant RSV strains should be avoided until new and effective prophylactic options also become available for this vulnerable population. Constant surveillance for new mutations and variations in RSV sequences will be critical to ensure that current mAbs remain effective against circulating RSV strains while vaccines begin to enter the market.”